The development of an effective vaccine against Plasmodium falciparum malaria could alleviate one of the most significant public health problems world-wide. There is clearly a need to identify new plasmodial antigens which can induce protection against blood-stage malaria. We have taken a strict immunization-based approach to this problem. Using the Plasmodium yoelii model to test several crude blood stage antigen and adjuvant combinations, we have established a system of vaccine induced immunity to blood-stage malaria infection. Solid protection against non- lethal and lethal P. yoelii challenge infection have been achieved. We have constructed P. yoelii genomic and cDNA expression libraries and selected recombinants based on the immune response of animals immunized and protected against P. yoelii infection. The major focus of this proposal will be the evaluation of the vaccine potential of selected recombinant antigens, and a detailed analysis of protective plasmodial antigens and the genes which encode them. The specific goals of this project are 1) to test purified recombinant antigens from selected cDNA clones for their ability to immunize mice against non-lethal and lethal P. yoelii infection as well as heterologous challenge infection; 2) to characterize protective P. yoelii antigens in detail, by identifying and localizing their corresponding native proteins, by obtaining their full- length gene sequence and by assessing their possible function in the biology of the parasite; 3) to begin to -characterize the immune response to protective P. yoelii antigens by determining the antigen specific profile of cytokine production (IL-2, IFN-gamma, IL-4, IL-10) by T cells and the isotypic profile of antigen specific antibodies in sera obtained from mice immunized with protective recombinant antigens, both before and after challenge infection with P. yoelii. Our long term objective is to use the information gained to clone homologous antigen genes from P. falciparum, with the goal of constructing a similar multivalent blood- stage vaccine against human malaria.